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Intermittent Fasting as Part of the Management for T2DM: from Animal Models to Human Clinical Studies

  • Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (B Conway and H Keenan, Section Editors)
  • Published:
Current Diabetes Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Diet is a pillar of type 2 diabetes mellitus (T2DM) management. Intermittent fasting (IF) is postulated as a novel approach, able to improve glucose control and potentially capable of reversing some of the pathophysiological alterations of this condition. In this review, the molecular and clinical evidence of diets based on intermittent energy restriction (IER) in laboratory animal models and subjects with type 2 diabetes is discussed. The mechanisms through which IF are thought to improve glucose homeostasis and reverse β cell failure are also reviewed.

Recent Findings

Studies derived from murine models suggest that IER is associated with improvements in β cell function and insulin resistance. Two main mechanisms have been demonstrated, one derived from the autophagy-lysosome pathway and, the other from an increase in neurogenin3 (Ngn3) levels (a marker for endocrine progenitor cells like β cells during development). Notably, IER also promotes reconstruction of gut microbiota. In mice, all effects were independent of weight loss. By contrast, in human studies, outcomes are widely attributable to weight loss. The more consistent results are reductions in body weight, visceral fat, and glucose and insulin levels. Increases in HDL cholesterol levels are also frequently reported. The decrease in insulin levels observed in humans is in opposition with the increase reported in mice, suggesting that the main mechanism in humans is an improvement in peripheral insulin action.

Summary

Recommending diets based on intermittent fasting in humans is based on the promising results found in animal models where an improvement in β cell function has been recorded. β cell function after IF has not been assessed in human subjects with T2DM. This review provides information regarding different protocols for the implementation of IF in diabetic persons and also provides important safety advice in order to avoid adverse effects. Clinical studies do not show an increased risk of hypoglycemia, and a recent case series reported reversal of T2DM.

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Abbreviations

ADF:

Alternate-day fasting

AL:

Ad libitum

ALT:

Alanine aminotransferase

ASUI:

Asthma Symptom Utility Index

AST:

Aspartate aminotransferase

BDNF:

Brain-derived neurotrophic factor

BF:

Body fat

BMI:

Body mass index

BW:

Body weight

BUN:

Blood urea nitrogen

CER:

Continuous energy restriction

CRP:

C-reactive protein

CV:

Cardiovascular

DBP:

Diastolic blood pressure

FFA:

Free fatty acid

FI:

Food intake

FT:

Fat tissue

FEV1:

Forced expiratory volume-1 minute

FGF21:

Fibroblast growth factor 21

FM:

Fat mass

FFM:

Fat-free mass

GH:

Growth hormone

GLP-1:

Glucose-like peptide type 1

GSK-3:

Glycogen synthase kinase 3

HDL-C:

High-density lipoprotein cholesterol

HOMA-IR:

Homeostasis model assessment insulin resistance

HADS:

Hospital Anxiety and Depression Scale

HbA1c:

Glycated hemoglobin

HR:

Heart rate

IER:

Intermittent energy restriction

IER-PF:

Intermittent energy restriction plus protein and fat ad libitum

IF:

Intermittent fasting

IFCR-F:

Intermittent fasting + caloric restriction + food based

IFCR-L:

Intermittent fasting + caloric restriction + liquid meals

IGF:

Insulin-like growth factor

IL-6:

Interleukin 6

LBM:

Lean body mass

LDL-C:

Low-density lipoprotein cholesterol

MiniAQLQ:

Mini Asthma Quality of Life Questionnaire

mTOR:

Mammalian target of rapamycin

PEF:

Peak expiratory flow

PPAR:

Peroxisome proliferator-activated receptors

REE:

Respiratory energy expenditure

SBP:

Systolic blood pressure

SHBG:

Sex hormone–binding globulin

SMBG:

Self-monitoring blood glucose

CSN:

Central nervous system

T2DM:

Type 2 diabetes mellitus

TC:

Total cholesterol

TCA:

Tricarboxylic acid

TG:

Triglycerides

TNF-α:

Tumoral necrosis factor-alpha

VLDL-C:

Very low-density lipoprotein cholesterol

vs:

Versus

WHO-5:

World Health Organization 5 Well-Being Index

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Authors and Affiliations

  1. Metabolic Diseases Research Unit, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico

    Liliana Muñoz-Hernández, Ziomara Márquez-López, Roopa Mehta & Carlos Alberto Aguilar-Salinas

  2. Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico

    Liliana Muñoz-Hernández

  3. Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Monterrey, Mexico

    Carlos Alberto Aguilar-Salinas

  4. Division of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion, Vasco de Quiroga #15, Tlalpan, 14080, Mexico City, Mexico

    Carlos Alberto Aguilar-Salinas

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  1. Liliana Muñoz-Hernández
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Muñoz-Hernández, L., Márquez-López, Z., Mehta, R. et al. Intermittent Fasting as Part of the Management for T2DM: from Animal Models to Human Clinical Studies. Curr Diab Rep 20, 13 (2020). https://doi.org/10.1007/s11892-020-1295-2

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